Planned obsolescence in humans and in other biosystems.

Abstract

PERSPECTIVES IN BIOLOGY AND MEDICINE Volume 29 ¦ Number 2 ¦ Winter 1986 PLANNED OBSOLESCENCE IN HUMANS AND IN OTHER BIOSYSTEMS ERNEST BEUTLER* The modern business school graduate speaks glibly of "planned obsolescence " as though the technique of building things not to last were something big business had invented only recently. But biosystems have developed this technique over millions of years, apparently as a result of another method more recently adopted by the business community, a careful cost-benefit analysis. Examination of the way that proteins, cells, and complete organisms have evolved suggests that for the individual and for the species as a whole planned destruction of parts that have reached a certain age may be the best way. Evolution has apparently made a cost-benefit analysis in deciding the fate of individual macromolecules. The cost of devising repair and maintenance mechanisms has been compared with the cost of merely remaking the molecule. The answer seems to have been that repair is worth a high price for DNA. Quite understandably, it seems advantageous to pay handsomely for elaborate repair mechanisms designed to preserve the fidelity of the genetic code. Minor changes seem sufficient to destroy the entire organism by activating an oncogene and producing a neoplasm [I]. Even here there seems to be a limit to what is worth doing. It is possible to speculate, on the basis of recent findings [2], that a suicide mechanism is brought into play when the number of chromosome This publication is number 3837-BCR from the Research Institute of Scripps Clinic. The work was supported in part by grant HL 25552 from the National Institutes of Health, Division of Heart, Lung, and Blood. *Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, La Jolla, California 92037.© 1986 by The University of Chicago. All rights reserved. 003 1-5982/86/2902-0469$0 1 .00 Perspectives in Biology and Medicine, 29, 2 · Winter 1986 \ 175 breaks in cells reaches a critical level. It is better to self-destruct than to take a chance that the repair task was not well done because of its magnitude . In contrast to the mechanisms that have worked to repair DNA, those that exist for the repair of proteins seem to be much more limited; planned obsolescence seems to be the approach that has won out. Some repair is possible. Oxidized methionines [3] and mixed disulfides [4] can be reduced, and racemized aspartic acid residues may be converted to their original form through a methylation process [5]. In general, however , damaged proteins are replaced rather than repaired. To make room for newly synthesized protein molecules, the old ones must be removed and their amino acids made available for recycling. This seems to be achieved via an elaborate group of widely distributed proteases and peptidases [6]. How are protein molecules selected for destruction? It is possible, of course, that proteolysis is merely a stochastic event—that the probability that any protein molecule will meet destruction is the same as that for any other molecule of that type. But the destruction of newly formed proteins would seem to be a very inefficient way to make room for more newly formed proteins. When a protein molecule does become damaged and changes its conformation from the native state, it becomes susceptible to proteolysis. However, it is probably more efficient to replace a tissue cell before it is functionally impaired. How this is achieved is not well understood, but there are some hints as to what may happen. The amino groups of asparagine and of glutamine are quite labile in general, even when the amino acids are incorporated into a peptide chain. The hydrolysis of these groups appears to be a chance event, and the probability that hydrolysis occurs is strongly influenced by the chemical groupings in the neighborhood of the amino acids [7]. It has been suggested that the latter may serve as the biologic clocks that determine when a protein is ready for replacement [7]. Midelfort and Mehler [8] were able to show that the five isozymes of aldolase A are tetramers composed of subunits that had either asparagine or aspartic acid in position near the carboxyl...